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Introduction: Cancer diagnosis influences the choices that patients make regarding current and future labor market activity. These choices have implications for governments based on resulting changes in taxes paid and benefits received. In this analysis we explore how human growth receptor 2 (HER2)-positive residual invasive breast cancer and different treatments influence government accounts excluding health costs. Methods: HER2-positive early breast cancer (eBC) health states from a published disease model were used to establish likelihood of working and wage impact at different stages of disease. The indirect productivity losses for an average woman aged 49 years were translated into fiscal consequences to government by applying an established government perspective-modeling framework. The fiscal projections (discounted) include gross tax revenue by disease stage, government transfer costs related to time off work and early retirement ,and net fiscal balance (e.g., gross taxes—transfers) in three countries Canada, Portugal, and Brazil. Results: The net fiscal balance in Canada for a healthy woman was C$109,551 compared with a HER2-positive eBC woman treated with trastuzumab emtansine (C$69,767) or trastuzumab (C$62,971). A similar pattern was observed in the three countries but reflecting the overall tax burden in each country, labor force activity, and available public benefits. Age at diagnosis was an important determinant of the likely net fiscal balance, as this influences the remaining working years. Discussion: Women diagnosed with HER2-positive eBC were estimated to pay less lifetime gross taxes and receive more in sickness benefits compared with healthy women. Treatments that improve outcomes are likely to offer fiscal gains for government from improved work force participation. [ABSTRACT FROM AUTHOR]

Simple Summary: In clinical practice, human epidermal growth factor receptor (HER2)-negative tumors include triple-negative or luminal breast cancer. HER2-negative breast cancer can be further characterized by immunohistochemical (IHC) and in situ hybridization (ISH) scores into HER2 IHC0 or HER2-low (IHC 1+, 2+/ISH−. Interest in HER2-low tumors has increased as data show the efficacy of HER2-targeted therapies in this subgroup. While several studies have examined treatment variations in the overall breast cancer population, there is limited information on the real-world treatment patterns among patients with HER2 (IHC0/-low) metastatic or recurrent breast cancer. Our study addresses this gap by analyzing treatment and outcomes by HER2 status and found that outcomes were similar in the HER2 IHC0 and -low groups. Our findings add value to the general understanding of the clinical differences between HER2 IHC0/-low and de novo/recurrent disease and have important implications for new effective treatment strategies designed for varying levels of HER2 expression. Improved understanding of the biological heterogeneity of breast cancer (BC) has facilitated the development of more effective and personalized approaches to treatment. This study describes real-world evidence on treatment patterns and outcomes for a population-based cohort of patients with human epidermal growth factor receptor (HER2) IHC0 and -low BC with de novo or recurrent disease from Alberta, Canada. Patients 18+ years old diagnosed with HER2 IHC0/-low, de novo/recurrent BC from 2010 to 2019 were identified using Alberta's cancer registry. Analyses of these patients' existing electronic medical records and administrative claims data were conducted to examine patient characteristics, treatment patterns, and survival outcomes. A total of 3413 patients were included in the study, of which 72.10% initiated first line hormonal and non-hormonal systemic therapy. The 1-year overall survival (OS) was 81.09% [95% CI, 79.52–82.69]. Recurrent patients had a higher OS compared to de novo patients: 54.30 months [95% CI, 47.80–61.90] vs. 31.5 months [95% CI, 28.40–35.90], respectively. Median OS was 43.4 months [95% CI, 40.70–47.10] and 35.80 months [95% CI, 29.00–41.70] among patients with HER2-low and HER2 IHC0 cancer, respectively. The study results provide real-world evidence regarding the clinical outcomes of HER2 IHC0/-low and de novo/recurrent disease. [ABSTRACT FROM AUTHOR]

Simple Summary: Around 25% of patients who undergo an ultrasound-guided thyroid biopsy end up with an indeterminate result based on cytology. This has propelled the use of other modalities, such as molecular testing, to further stratify these patients. The aim of our retrospective study was to report and compare two genetic mutations in our patient population. These mutations are RET/PTC and THADA/IGF2BP3 translocations, which have been hypothesized as oncogenic events in thyroid neoplasms. We confirm that our patient population exhibited these mutations, and all underwent a final histopathology analysis where surgery was the preferred treatment modality. We also report that the RET/PTC fusion exhibited more aggressive features than the THADA/IGF2BP3 fusion and was more likely to need post-surgical treatment. Background: Molecular testing has been used as an adjunct to morphological evaluation in the workup of thyroid nodules. This study investigated the impact of two gene fusions, RET/PTC and THADA/IGF2BP3, that have been described as oncogenic events in thyroid neoplasms. Methods: We performed a retrospective, single-centered study at a McGill University teaching hospital in Montreal, Canada, from January 2016 to August 2021. We included patients who underwent surgery for thyroid nodules that pre-operatively underwent molecular testing showing either RET/PTC or THADA/IGF2BP3 gene fusion. Results: This study included 697 consecutive operated thyroid nodules assessed using molecular testing, of which five had the RET/PTC fusion and seven had the THADA/IGF2BP3 fusion. Of the five nodules in the RET/PTC group, 100% were malignant and presented as Bethesda V/VI. Eighty percent (4/5) were found to have lymph node metastasis. Twenty percent (1/5) had extrathyroidal extensions. Sixty percent (3/5) were a diffuse sclerosing variant of papillary thyroid carcinoma, and the rest were the classical variant. Of the seven THADA/IGF2BP3 nodules, all presented as Bethesda III/IV and 71.4% (5/7) were malignant based on the final pathology analysis, and 28.6% (2/7) were NIFTP. All the THADA/IGF2BP3 fusion malignancies were a follicular variant of papillary thyroid carcinoma. None had lymph node metastasis or displayed extrathyroidal extensions. Conclusions: RET/PTC nodules presented as Bethesda V/VI and potentially had more aggressive features, whereas THADA/IGF2BP3 nodules presented as Bethesda III/IV and had more indolent behavior. This understanding may allow clinicians to develop more targeted treatment plans, such as the extent of surgery and adjuvant radioactive iodine treatment. [ABSTRACT FROM AUTHOR]

PURPOSE The identification of BRAF mutations in melanoma enables targeted therapy and improves patient outcomes. Barriers to BRAF molecular testing affect the quality of care and therapeutic options. METHODS This retrospective study mapped BRAF testing timelines in adult patients with melanoma at the Princess Margaret Cancer Centre to identify obstacles to timely BRAF reporting and its impact on the initiation of therapy. RESULTS Sixty-six cases were included. The median time between BRAF request and result was 12 days (95% CI, 8 to 15) when the BRAF test was ordered by pathology, compared with 20 days (95% CI, 16 to 23) if the test was requested by another specialist (P, .001). When the BRAF test and biopsy were performed within the same institution, the BRAF median turnaround time (TAT) was 13 days (95% CI, 6 to 19) compared with 19 days (95% CI, 16 to 21) if the sample was transferred from another institution (P5.02). Forty-seven patients received systemic therapy, and 20 had metastatic disease. In the metastatic subgroup, if the BRAF result was available at the first medical oncology visit, the initiation of treatment was 20 days (95% CI, 9.6 to 30.3), but was delayed to 31 days (95% CI, 10.8 to 51.1) if the BRAF result was not available (P 5 .03). CONCLUSION This study showed variations in BRAF test results in TAT. One factor affecting this timeline is the transfer time, which can be streamlined by pathology reflex testing. Delays in TAT affect the timing and type of therapeutic intervention, especially in patients with stage IV disease. [ABSTRACT FROM AUTHOR]

The management of patients with hormone receptor-positive breast cancer has changed dramatically with use of the 21-gene Recurrence Score® (RS) Assay. While the utility of the assay was initially demonstrated among node-negative patients, recent studies have also demonstrated the assay's prognostic and predictive value in node-positive patients. In Canada, the RS assay is reimbursed by provincial health insurance plans, but not all provinces have approved the use of the assay for patients with node-positive disease. Here, we provide an overview of the clinical factors that influence physician recommendation of the RS assay and, alternatively, the impact of the RS assay on patient treatment decisions in Canada. We performed a comprehensive review of the impact of the assay upon physician treatment decisions and cost in node-positive breast cancer patients within Canada and other countries. Furthermore, we evaluated biomarkers that can predict the RS result, in addition to other genomic assays that predict recurrence risk among node-positive patients. Overall, the 21-gene RS assay was shown to be a cost-effective tool that significantly reduced the use of chemotherapy in node-positive breast cancer patients in Canada. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer among women worldwide and the second leading cause of brain metastases (BrM). We assessed the treatment patterns and outcomes of women treated for breast cancer BrM at our institution in the modern era of stereotactic radiosurgery (SRS). Materials and Methods: We conducted a retrospective analysis of women (≥18 years of age) with metastatic breast cancer who were treated with surgery, whole brain radiotherapy (WBRT), or SRS to the brain at the Sunnybrook Odette Cancer Centre, Toronto, Canada, between 2008 and 2018. Patients with a history of other malignancies and those with an uncertain date of diagnosis of BrM were excluded. Descriptive statistics were generated and survival analyses were performed with subgroup analyses by breast cancer subtype. Results: Among 683 eligible patients, 153 (22.4%) had triple‐negative breast cancer, 188 (27.5%) had HER2+, 246 (36.0%) had hormone receptor (HR)+/HER2−, and 61 (13.3%) had breast cancer of an unknown subtype. The majority of patients received first‐line WBRT (n = 459, 67.2%) or SRS (n = 126, 18.4%). The median brain‐specific progression‐free survival and median overall survival (OS) were 4.1 months (interquartile range [IQR] 1.0–9.6 months) and 5.1 months (IQR 2.0–11.7 months) in the overall patent population, respectively. Age >60 years, presence of neurological symptoms at BrM diagnosis, first‐line WBRT, and HER2− subtype were independently prognostic for shorter OS. Conclusion: Despite the use of SRS, outcomes among patients with breast cancer BrM remain poor. Strategies for early detection of BrM and central nervous system–active systemic therapies warrant further investigation. Implications for Practice: Although triple‐negative breast cancer and HER2+ breast cancer have a predilection for metastasis to the central nervous system (CNS), patients with hormone receptor–positive/HER2− breast cancer represent a high proportion of patients with breast cancer brain metastases (BrM). Hence, clinical trials should include patients with BrM and evaluate CNS‐specific activity of novel systemic therapies when feasible, irrespective of breast cancer subtype. In addition, given that symptomatic BrM are associated with shorter survival, this study suggests that screening programs for the early detection and treatment of breast cancer BrM warrant further investigation in an era of minimally toxic stereotactic radiosurgery. Despite advances in treatment, the prognosis of patients with breast cancer brain metastasis remains poor. This article assesses treatment patterns and outcomes of such patients in the modern era of stereotactic radiosurgery. [ABSTRACT FROM AUTHOR]

Importance: Combining biologic monoclonal antibodies with chemotherapeutic cytotoxic drugs provides clinical benefit to patients with advanced or metastatic colorectal cancer, but the optimal choice of the initial biologic therapy in previously untreated patients is unknown.Objective: To determine if the addition of cetuximab vs bevacizumab to the combination of leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6) regimen or the combination of leucovorin, fluorouracil, and irinotecan (FOLFIRI) regimen is superior as first-line therapy in advanced or metastatic KRAS wild-type (wt) colorectal cancer.Design, Setting, and Participants: Patients (≥18 years) enrolled at community and academic centers throughout the National Clinical Trials Network in the United States and Canada (November 2005-March 2012) with previously untreated advanced or metastatic colorectal cancer whose tumors were KRAS wt chose to take either the mFOLFOX6 regimen or the FOLFIRI regimen as chemotherapy and were randomized to receive either cetuximab (n = 578) or bevacizumab (n = 559). The last date of follow-up was December 15, 2015.Interventions: Cetuximab vs bevacizumab combined with either mFOLFOX6 or FOLFIRI chemotherapy regimen chosen by the treating physician and patient.Main Outcomes and Measures: The primary end point was overall survival. Secondary objectives included progression-free survival and overall response rate, site-reported confirmed or unconfirmed complete or partial response.Results: Among 1137 patients (median age, 59 years; 440 [39%] women), 1074 (94%) of patients met eligibility criteria. As of December 15, 2015, median follow-up for 263 surviving patients was 47.4 months (range, 0-110.7 months), and 82% of patients (938 of 1137) experienced disease progression. The median overall survival was 30.0 months in the cetuximab-chemotherapy group and 29.0 months in the bevacizumab-chemotherapy group with a stratified hazard ratio (HR) of 0.88 (95% CI, 0.77-1.01; P = .08). The median progression-free survival was 10.5 months in the cetuximab-chemotherapy group and 10.6 months in the bevacizumab-chemotherapy group with a stratified HR of 0.95 (95% CI, 0.84-1.08; P = .45). Response rates were not significantly different, 59.6% vs 55.2% for cetuximab and bevacizumab, respectively (difference, 4.4%, 95% CI, 1.0%-9.0%, P = .13).Conclusions and Relevance: Among patients with KRAS wt untreated advanced or metastatic colorectal cancer, there was no significant difference in overall survival between the addition of cetuximab vs bevacizumab to chemotherapy as initial biologic treatment.Trial Registration: clinicaltrials.gov identifier: NCT00265850. [ABSTRACT FROM AUTHOR]

The article presents the adaptation of Cancer Care Ontario's guidelines on optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancers. The involvement of the American Society of Clinical Oncology (ASCO), the value of cytotoxic chemotherapy, and the anthracycline-taxane regimen.

Rationale, aims and objectives Despite multiple guidelines advocating against routine radiological evaluation for metastases in women with early stage breast cancer, imaging is still frequently overused. The objective of this study was to assess doctor's views on imaging guidelines, and an attempt to establish why personal and local clinical practice patterns regarding imaging may differ from current guidelines. Methods Canadian doctors who treat breast cancer were invited by email to complete an online survey developed by members of the research team. Results Responses were received from 173 physicians (26% response rate). Most (82%) indicated awareness of at least one published imaging guideline. Sixty per cent indicated that they had read the recommendations of the 2012 American Society of Clinical Oncology ' Top 5' list for choosing wisely in oncology imaging and, of those, 81% agreed with it. However, most indicated that this recommendation has not influenced them to order less imaging. Over 95% of doctors identified suspicious history, physical examination findings and inflammatory breast cancer as important factors for performing imaging. The majority did not feel that patient demand, fear of litigation or ease of access to imaging influenced their ordering for imaging. Conclusions The majority of breast cancer doctors are aware of and generally agree that guidelines pertaining to staging imaging for early breast cancer are reflective of evidence. Despite this, adherence is variable and factors such as local practice patterns and disease biology may play a role. Alternative strategies, beyond simply publishing recommendations, are therefore required if there is to be a sustained change in doctor behaviour. [ABSTRACT FROM AUTHOR]

This article discusses a study which examined the roles of the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and epidermal growth factor receptor (EGFR) as predictive biomarkers in patients with advanced pancreatic cancer who receive erlotinib. Researchers analyzed tumor samples for EGFR gene copy number (GCN) and KRAS mutation status in a subset of treated and control patients who were enrolled on a study by the National Cancer Institute of Canada Clinical Trials Group PA.3. The findings of the study are explored.

Background: Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population.Methods: We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects).Results: Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (<50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8. 48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1. 49-7.56).Conclusions: Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population. [ABSTRACT FROM AUTHOR]

Simple Summary: Reflex molecular testing is an emerging concept in oncology that, for a variety of cancers, was demonstrated to reduce the time to treatment initiation, thus potentially impacting survival outcomes. In advanced melanoma, BRAF mutation testing is critical in predicting treatment response with targeted therapy (i.e., BRAF/MEK inhibitors). Certain features were identified in melanomas that harbor BRAF mutations (e.g., primary lesions located on the trunk, diagnosed in patients <50, visibly pigmented tumors and, at times, with ulceration or specific dermatoscopic features). For select advanced melanoma patients, delays in determining mutational status present a significant barrier to the prompt initiation of treatment, which can adversely impact patient outcomes, especially in the metastatic setting due to a rapidly progressive disease. Treatment in these cases needs to start promptly by a medical oncologist. Ordering BRAF testing by preceding members of the treating team will allow medical oncologists to initiate treatment at the first visit. According to poor survival outcomes, we propose that patients with thick tumors (>4.0 mm) or >2 mm tumors with ulceration (i.e., stage ≥IIB) should potentially be considered for systemic therapy, thus justifying reflex BRAF testing. We overview current BRAF mutation testing recommendations and methods used in the United States, Canada, and Europe. Targeted therapy has been developed through an in-depth understanding of molecular pathways involved in the pathogenesis of melanoma. Approximately ~50% of patients with melanoma have tumors that harbor a mutation of the BRAF oncogene. Certain clinical features have been identified in BRAF-mutated melanomas (primary lesions located on the trunk, diagnosed in patients <50, visibly pigmented tumors and, at times, with ulceration or specific dermatoscopic features). While BRAF mutation testing is recommended for stage III–IV melanoma, guidelines differ in recommending mutation testing in stage II melanoma patients. To fully benefit from these treatment options and avoid delays in therapy initiation, advanced melanoma patients harboring a BRAF mutation must be identified accurately and quickly. To achieve this, clear definition and implementation of BRAF reflex testing criteria/methods in melanoma should be established so that patients with advanced melanoma can arrive to their first medical oncology appointment with a known biomarker status. Reflex testing has proven effective for a variety of cancers in selecting therapies and driving other medical decisions. We overview the pathophysiology, clinical presentation of BRAF-mutated melanoma, current guidelines, and present recommendations on BRAF mutation testing. We propose that reflex BRAF testing should be performed for every melanoma patient with stages ≥IIB. [ABSTRACT FROM AUTHOR]

Profiles Dr. Arun Seth, professor of the Department of Laboratory Medicine and Pathobiology at the University of Toronto. Highlights of his achievements in the field of Molecular Oncology; Focus on his work on the 'mos oncogene'; Development of high throughput diagnostic tools for molecular staging of breast tumors.

Organized screening has contributed to a decline in cervical cancer incidence and mortality over the past 50 years. However, women in developing countries are yet to profit extensively from the benefits of screening programs, and recent trends show a resurgence of the disease in developed countries. The past 2 decades have witnessed substantial progress in our understanding of the natural history of cervical cancer and in major treatment advances. Human papillomavirus (HPV) infection is now recognized as the main cause of cervical cancer, the role of coexisting factors is better understood, a new cytology reporting terminology has improved diagnosis and management of precursor lesions, and specific treatment protocols have increased survival among patients with early or advanced disease. Current research has focused on the determinants of infection with oncogenic HPV types, the assessment of prophylactic and therapeutic vaccines and the development of screening strategies incorporating HPV testing and other methods as adjunct to cytology. These are fundamental stepping stones for the implementation of effective public health programs aimed at the control of cervical cancer.